Adsorption of Toll-Like Receptor 4 Agonist to Alum-Based Tetanus Toxoid Vaccine Dampens Pro-T Helper 2 Activities and Enhances Antibody Responses

• Published in: Journal of immunology research 2015-01, Vol.2015 (2015), p.1-9
• Main Authors: Gomes, E., Rodriguez, Dunia, Mirotti, Luciana, Bortolatto, Juliana, Russo, Momtchilo
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Adsorption; Allergies; Alum Compounds; Animals; Antibody Formation - immunology; Antigens; Antigens, Bacterial - immunology; Asthma; Bronchoalveolar Lavage Fluid - immunology; Dendritic cells; Diphtheria; Disease Models, Animal; Escherichia coli; Female; Hypersensitivity - immunology; Hypersensitivity - metabolism; Immunization; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulins; Immunology; Ligands; Lipopolysaccharides - immunology; Lipopolysaccharides - pharmacology; Mice; Ovalbumin - immunology; Poly I-C - immunology; Poly I-C - pharmacology; Salmonella minnesota; Studies; Tetanus; Tetanus Antitoxin - immunology; Tetanus Toxoid - immunology; Th2 Cells - immunology; Th2 Cells - metabolism; Toll-Like Receptor 3 - antagonists & inhibitors; Toll-Like Receptor 3 - metabolism; Toll-Like Receptor 4 - agonists; Toll-Like Receptor 4 - metabolism; Vaccines; Whooping cough
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2015/280238

Aluminum salts gels (alum) are TLR-independent adjuvants and have been used to boost antibody responses in alum-based vaccines such as diphtheria, pertussis, and tetanus toxoid (DPT) triple vaccine. However, the pro-Th2 activity of alum-based vaccine formulations has not been fully appreciated. Here we found that alum-based tetanus toxoid (TT) vaccine was biased toward a Th-2 profile as shown by TT-induced airway eosinophilic inflammation, type 2 cytokine production, and high levels of IgE anaphylactic antibodies. The adsorption into alum of prototypic TLR4 agonists such as lipopolysaccharides (LPS) derived from Escherichia coli consistently dampened TT-induced Th2 activities without inducing IFNγ or Th1-like responses in the lung. Conversely, adsorption of monophosphoryl lipid A (MPLA) extracted from Salmonella minnesota, which is a TIR-domain-containing adapter-inducing interferon-β- (TRIF-) biased TLR4 agonist, was less effective in decreasing Th-2 responses. Importantly, in a situation with antigenic competition (OVA plus TT), TT-specific IgG1 or IgG2a was decreased compared with TT sensitization. Notably, LPS increased the production of IgG1 and IgG2a TT-specific antibodies. In conclusion, the addition of LPS induces a more robust IgG1 and IgG2a TT-specific antibody production and concomitantly decreases Th2-cellular and humoral responses, indicating a potential use of alum/TLR-based vaccines.